Development of a sustained release dosage form for alpha-lipoic acid. I. Design and in vitro evaluation.

The purpose of this study was the design and evaluation of a sustained release dosage form for the oral administration of alpha-lipoic acid. The cationic polymer chitosan was used in order to provide a controlled drug release based on ionic interactions with the anionic drug. The effect of such ionic interactions on the release of alpha-lipoic acid could be verified by diffusion studies. In vitro release studies with tablets (diameter: 10.0 mm; thickness: approximately 4 mm) containing 80% alpha-lipoic acid and 20% chitosan acetate showed a controlled drug release over a time period of 24 h. Raising the ratio of chitosan acetate in such delivery systems led to an even stronger retardation of drug release. In addition, permeation studies carried out in Ussing-type chambers with freshly excised intestinal mucosa from guinea pigs demonstrated no significant (p < 0.05) influence of the degree of drug ionization on its absorption behavior. The apparent permeability coefficient (Papp) for alpha-lipoic acid was determined to be 1.39 +/- 0.28 x 10(-5) cm/sec at pH 6.4 (means +/- SD). The use of a sustained delivery system for alpha-lipoic acid, which is based on ionic interactions, should therefore have no influence on the absorption behavior of the drug. The sustained release dosage forms described here might provide a constant plasma level of the drug being highly beneficial for various therapeutic reasons.

Development of a sustained release dosage form for alpha-lipoic acid. II. Evaluation in human volunteers.

Within this study an oral sustained release dosage form of alpha-lipoic acid (thioctic acid) has been generated and evaluated in healthy volunteers. A granulate comprising 56.8% alpha-lipoic acid and 43.2% chitosan acetate was compressed to tablets (weight: 0.45 g; diameter: 10.0 mm; thickness: 4 mm). Three of these tablets were administered at once orally to each volunteer. Prior to administration and then every hour for 12 hours blood samples were taken from the antebrachial vein. alpha-Lipoic acid concentrations in plasma were quantified via precolumn derivatization and reversed-phase high-performance liquid chromatography (HPLC). Results demonstrated that an increased plasma level of alpha-lipoic acid can be achieved by this formulation for at least 12 hours. Within this time period at least two maximum plasma concentrations were reached. The first one is based on the release of alpha-lipoic acid, which is not ionically and therefore only loosely bound to chitosan, whereas a second maximum is based on the release of the drug during the enzymatic degradation of the chitosan matrix in the colon. The AUC(0-12) was determined to be 183.8 +/- 101.4 microg x min/mL (mean +/- SD; n = 8). Because of the pulsed sustained release of alpha-lipoic acid, the dosage form described here seems to be highly beneficial in order to stimulate the glucose uptake in the case of diabetes type II.